The major emphasis of this project is the elucidation of the genetic structure of recombinant viruses derived after inoculation of mice with exogenous ecotropic murine leukemia viruses (MuLVs). Such recombinants, termed mink cell focus-forming viruses (MCFs), exhibit an altered host range and are thought to be involved in the pathogenesis of MuLVs. In the initial studies, MCFs derived from NFS mice after inoculation of an erythroleukemia virus (F-MuLV 57) or a lymphocytic leukemia virus (M-MuLV 1387) were examined. It was found that F-MuLV 57 recombined with two distinct endogenous retrovirus sequences and that M-MuLV recombined with a third sequence distinct from the sequence found in recombinants with F-MuLV 57. Further studies indicated that a different strain of F-MuLV (F-MuLV 87) recombines with a sequence which is distinct from the endogenous sequences of F-MuLV 57-derived MCFs but may be identical to sequences found in M-MCFs. These results indicate that a given MuLV preferentially recombines with a specific endogenous retroviral sequence(s) in NFS mice to generate MCFs. One group of MCFs derived from F-MuLV 57 was found to be much more infectious for mink cells than for mouse (SC-1) cells. This group also exhibited an altered Fv-1 tropism (B-tropic) compared to F-MuLV 57 (NB-tropic). All other MCFs in these studies were equally infectious for mink and SC-1 cells and retained the Fv-1 tropism of the ecotropic parent. None of the MCFs derived from F-MuLV 57 or F-MuLV 87 was found to be oncogenic while the M-MCFs induced lymphocytic leukemia in NFS and AKR mice. Examination of MCFs derived from an in vitro constructed recombinant between the F-MuLV 57 and the amphotropic virus 4070A indicated that sequences other than the env gene determine the specificity of recombination of MuLVs.